D-arginine is an essential ingredient used for producing medicaments such as an enuresis therapeutic agent Desmopressin, a hereditary angioedema therapeutic agent Icatibant, and a hyperparathyroidism therapeutic agent Velcalcetide.
Conventional techniques for preparing D-arginine are largely classified into two types, one of which is a biological optical resolution process using an enzyme, and the other of which is a chemical optical resolution process using a chiral organic acid.
A method of preparing D-arginine through a biological optical resolution, including selectively obtaining D-acetyl-arginine from DL-acetyl-arginine through a optical resolution using an enzyme and then hydrolyzing the D-acetyl-arginine, is known in [Archives of Biochemistry Biophysics, 39, 108(1952); Archives of Biochemistry Biophysics, 60, 496(1956); The Journal of Biochemistry, 45(9), 687 (1958)], but is problematic because many process steps are performed and the hydrolysis of D-acetyl-arginine, obtained through optical resolution, corresponding to a key step, in a hydrochloric acid aqueous solution is required.
As an additional enzyme-assisted technique, U.S. Pat. No. 5,591,613 discloses a method of preparing D-arginine by selectively decomposing L-arginine of DL-arginine into L-ornithine using an enzyme. However, this method is disadvantageous in that L-arginine contained in DL-arginine is not recovered but is decomposed.
On the other hand, a chemical optical resolution using a chiral organic acid is advantageous in that chemical processing is performed using a simple apparatus and is easy, compared to biological processing, and is thus suitable for mass production. Here, appropriately selecting the chiral organic acid that serves as the optical resolving agent is very important but is difficult.
Analytical Biochemistry, 63, 68(1975) has reported that, in order to prepare D-arginine from DL-arginine, optical resolving agents such as tartaric acid, camphoric acid and glutamic acid have been employed but have failed to obtain desired results, and also that D-arginine may be separated and obtained using L-malic acid. However, complicated processing, including crystallizing an aqueous solution of DL-arginine and L-malic acid for one day in a refrigerator to thus afford a primary crystal, which is then concentrated to give a secondary crystal, has to be carried out. In particular, only the specific optical rotation ([α]D) of the obtained D-arginine is mentioned, and instrumental analysis by chiral chromatography is not provided, making it difficult to accurately confirm the optical purity of the obtained D-arginine, which is undesirable.